This application is for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) - IU Clinical Center. Nonalcoholic fatty liver disease (NAFLD) affects one out of every three adults and five children in North America and is a growing public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), may lead to end-stage liver disease and primary liver cancer, as well as liver-, cardiovascular-, and cancer- related mortality, resulting in major increases in health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health significance of NASH that can only be addressed via a large research consortium. The primary objective of the NASH CRN is to perform clinical research on NASH and NAFLD in adults and children. A closely linked and high priority secondary objective is to conduct translational research in NASH and NAFLD focusing on the pathogenesis that will provide the basis for understanding the natural history and developing means of better diagnosis, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycle will be completed, and new therapeutic trials, including phase 2a proof of mechanism and phase 2b clinical trials will be initiated, to develop evidence-based treatment options that are safe, effective, simple, and inexpensive. The longitudinal cohort of adults and children with NAFLD will be extended, which will prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation, and development and validation of non-invasive techniques to evaluate and identify those with NASH/NAFLD, who will respond, and how quickly the disease is progressing. IU Clinical Center will actively participate in the (a) successful completion of the ongoing studies, (b) successful launching of new therapeutic trials and (c) development of new ancillary and publication proposals. In addition, IU Clinical Center investigators will actively participate in various committees including the Steering Committee, Ancillary Studies Committee, Genetics Subcommittee, Pediatrics Committee, Pathology Committee and Imaging Committee. IU Clinical Center is eager to continue its collaboration with other clinical centers, data coordinating center, NIDDK program staff, and private sector partners to complete these very important research objectives. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.